There has been an exponential increase in the rate of incidence of Parkinson's disease (PD) with aging in the global population. PD, the second most common neurodegenerative disorder, results from damaged dopamine neurons in the substantia nigra pars compacta (SNpc), along with the deposition of abnormal α-synuclein (α-Syn), and the progressive degeneration of neurons in striatal regions. Despite extensive investigations to understand the pathophysiology of PD to develop effective therapies to restrict its progression, there is currently no cure for PD. Puerarin (Pue) is a natural compound with remarkable anti-PD properties. However, its poor pharmacological properties, including poor water solubility, inadequate bioavailability, and incomplete penetration of the blood-brain barrier (BBB) have restricted its use for the treatment of PD. Nevertheless, advancements in nanotechnology have revealed the potential advantages of targeted drug delivery into the brain to treat PD. Here, we used Pue-loaded graphene oxide (GO) nanosheets, which have an excellent drug-loading ability, modifiable surface functional groups, and good biocompatibility. Then, Pue was transported across the BBB into the brain using lactoferrin (Lf) as the targeting ligand, which could bind to the vascular endothelial receptor on the BBB. In vivo and in vitro results indicated that this multifunctional brain targeted drug delivery system (Lf-GO-Pue) was an effective and safe therapy for PD.